The rapid intravenous administration of digitalis has recently been shown to cause a substantial increase in coronary vascular resistance in the normal heart. Our recent studies have demonstrated that this neurogenically mediated increase in coronary vascular resistance is potentially detrimental if it occurs during ischemia. These studies have been carried out using a model of acute global ischemia in dogs anesthetized with chloralose and urethane. Reducing coronary perfusion pressure to induce ischemia elevated left ventricular end diastolic pressure and resulted in negative myocardial lactate balance. Following intravenous acetylstrophanthidin coronary vascular resistance either showed erratic changes of progressive increases which terminated in ventricular fibrillation. The increases in coronary vascular resistance appeared secondary to alpha adrenergic receptor stimulation, erratic increases in coronary vascular resistance were also observed with intravenous digoxin during ischemia and these increases could be abolished with alpha adrenergic receptor blockade. Thus, intravenous digitalis in the ischemic heart results in increases in coronary vascular resistance mediated through alpha adrenergic receptor stimulation which are potentially detrimental. Studies on the efficacy of phenytoin administered directly into the cerebral spinal fluid in against digoxin-induced ventricular tachyarrhythmias have been initiated. Preliminary data indicate a higher survival rate in those animals which are pre-treated with intrathecal phenytoin before the administration of toxic doses of digoxin intravenously. Also, intrathecal phenytoin results in a significant prolongation of the time to ventricular ectopic activity, the time to ventricular tachycardia and the time to ventricular fibrillation following intravenous digoxin.